Recombinant Human Neuroendocrine convertase 1 (PCSK1)

1. we found eight known variants and two novel heterozygous variants (c.1095 + 1G > A and p.S24C), and identified and functionally characterized two rare novel PCSK1 variants of which c.1095 + 1G > A caused complete loss of protein function. In addition to confirming rs6232 and rs6234 in PCSK1 as polygenic risk variants for childhood obesity, we describe an association of rs725522 with insulin metabolism. PMID: 28271036
2. investigation of the pathogenesis of obesity in the PC1/3-N222D mouse model and whether this molecular mechanism also applies to common and rare human PCSK1 mutations PMID: 26786350
3. PCSK1 deficiency plays a role in human endocrinopathies, obesity, gastrointestinal disorders. PMID: 27187081
4. findings suggest that the major neuroendocrine features of Prader-Willi syndrome are due to PC1 deficiency PMID: 27941249
5. PCSK1 mutations are associated with Obesity. PMID: 27288825
6. PCSK1 expression is significantly upregulated in human masticatory mucosa during wound healing PMID: 28005267
7. these common variants in PCSK1 and POMC were not the major cause of obesity in the Thai subjects sampled. However, variants in PCSK1 did affect cholesterol level, LDL-C level, and waist circumference. PMID: 26345846
8. conclude that the N309K enzyme is able to cleave its own propeptide but is catalytically inert against in trans substrates, and that this variant accounts for the enteric and systemic endocrinopathies seen in the consanguineous kindred studied PMID: 25272002
9. we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology. PMID: 25784503
10. Data show that prohormone convertase 1/3 (PC1/3) endoplasmic reticulum-retained mutants induce endoplasmic reticulum stress. PMID: 26207343
11. Mechanism of Fine-tuning pH Sensors in Proprotein Convertases: IDENTIFICATION OF A pH-SENSING HISTIDINE PAIR IN THE PROPEPTIDE OF PROPROTEIN CONVERTASE 1/3. PMID: 26229104
12. rs6232 associated with body mass index PMID: 25031086
13. We showed for the first time that a nonsense mutation in PCSK1 was likely to cause dominantly inherited human obesity, due to the inhibiting properties of the propeptide fragment encoded by the null allele PMID: 24890885
14. Epistases between single nucleotide polymorphisms within proprotein convertase subtilisin/kexin type 1(PCSK1) and dopamine beta-hydroxylase(DBH) genes are significantly associated with susceptibility or resistance to premature ovarian failure PMID: 24618767
15. FTO-rs9939609, TMEM18-rs6548238 and PCSK1-rs6234 polymorphisms are significantly associated with body mass index in a southern Chinese population. PMID: 25189249
16. SNPs rs6232, rs6234, and rs6235 associated with obesity in Caucasians [review] PMID: 25355447
17. Common genetic variants in PCSK1 are associated with coronary artery disease in Chinese patients with type 2 diabetes. PMID: 24489861
18. PC1/3(S357G) exhibited a lower calcium dependence; a higher pH optimum. PMID: 24932808
19. PCSK1 is overexpressed in fibrolamellar hepatocellular carcinoma. PMID: 24443104
20. Thais carrying SNPs rs6234-5 are at increased risk of obesity, and the risk of severe obesity increases when carrying both rs6234-5 and rs3811951, but not with rs271939. Patients with genetic variations at rs3811951 are at risk of having low HDL-C levels. PMID: 24964673
21. PC1/3 overexpression induces morphological and phenotypic epithelial-mesenchymal transition changes of airway epithelial cells involved in the pathogenesis of nasal polyps PMID: 23314902
22. Data show the synthetic effect of SNPs on the indices of adiposity and risk of obesity in Chinese girls, but failed to replicate the effect of five separate variants of SEC16B rs10913469, SH2B1 rs4788102, PCSK1 rs6235, KCTD15 rs29941 and BAT2 rs2844479. PMID: 23121087
23. the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation. PMID: 23800642
24. Common PCSK1 variants (notably rs6232 and rs6235) contribute modestly to obesity in multi-ethnic American population. PMID: 23451278
25. study indicates that the PCSK1 rs6235 SNP may contribute to the risk of overweight in men and predict obesity-related metabolic traits such as waist circumference and diastolic blood pressure in Taiwanese subjects PMID: 24140494
26. The data of this study suggest that defects in the processing of hypothalamic neuropeptides in huntington disease may partially arise from decreased PC1/3 and PC2 expressions. PMID: 24226266
27. novel R80Q (rs1799904) variant both exhibits adverse effects on PC1/3 activity and is prevalent in the population PMID: 23383060
28. PCSK1 SNP rs6235 was associated with essential hypertension and blood pressure in the Han Chinese population PMID: 22592666
29. PCSK1 rs6232 is associated with childhood and adult class III obesity in the Mexican population PMID: 22737226
30. The potential variations in the exons and exon/intron junctions of caprine PC1 gene, were studied. PMID: 22552345
31. Our data suggest that SNPs in or near the PCSK1 locus contribute to obesity risk in the Greek population. PMID: 21720444
32. PCSK1 rs6232 G-allele and rs6235 C-allele have an effect on body composition which may be modified by sex PMID: 21935364
33. an increased risk of obesity in heterozygous carriers of mutations in the PCSK1 gene. PMID: 22210313
34. triple-variant prohormone convertase 1 underwent significantly more proteolytic processing at the N- and C-termini than the double-variant isoforms PMID: 22000902
35. common PCSK1 genetic variants are associated with obesity in the Chinese population PMID: 19875984
36. The rs6234 G-allele showed a significant association with increased risk of combined phenotype of obesity and overweight in Chinese. PMID: 20498726
37. Studies of protease SPC3 (PC1/3) suggest that C-domain sequences contribute to cleavage site selection for proinsulin PMID: 20106974
38. The presence of PC and GOAT in the cells, as well as n-octanoic acid in the culture medium, was necessary to produce n-octanoyl ghrelin. PMID: 19628676
39. prominently expressed in PTHrP-expressing human cancer cell lines originating from tumors of the breast, lung, prostate, as well as lymphoma PMID: 11720250
40. Polymorphism associated with insulin resistance affects insulin snssitivity by interacting with PPARgamma2. PMID: 14574455
41. PC1 is present in the human cortex to fulfill its role in proteolytic processing of neuropeptide precursors; no significant change in PC1 levels is observed in Alzheimer patients. PMID: 14614908
42. Data suggest that proprotein convertase 1, presumably in the enteroendocrine cells, is essential for the normal absorptive function of the human small intestine. PMID: 14617756
43. results have implications for the mechanism of granule sorting of PC3 as well as for the topology of PC2 and carboxypeptidase E, which have been reported to span the lipid membrane by homologous charged sequences PMID: 15807527
44. PC1 and PC2 in are abnormally expressed and processed in human colorectal liver metastases PMID: 16293189
45. PC1 has a role in obesity, hyperphagia and increased metabolic efficiency PMID: 16644867
46. A novel missense mutation Ser307Leu in PC 1/3 linked to hyperphagia and obesity. PMID: 17595246
47. defective PC1/3 expression may lead to preferential production of unprocessed, biologically inactive ACTH variants in sient corticotroph adenoma. PMID: 17917309
48. PC1/3 governs the endocrine and PC2 the neuronal processing of proCCK, whereas PC5/6 contributes only to a modest endocrine synthesis of CCK-22. PMID: 18096669
49. Suppression of Pdcd4 resulted in an increased release of CgA and Sg II and was accompanied by an up-regulation of intracellular PC1. PMID: 18549351
50. The nonsynonymous variants of PCSK1 rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children PMID: 18604207

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HGNC: 8743

OMIM: 162150

KEGG: hsa:5122

STRING: 9606.ENSP00000308024

UniGene: Hs.78977